Diagnosing iron deficiency is usually straightforward—until inflammation enters the picture. In patients with chronic infections, autoimmune disease, cancer, or renal failure, interpreting iron studies becomes a clinical minefield. The most commonly ordered marker, serum ferritin, is not just a storage protein for iron. It’s also an acute-phase reactant, meaning its levels can rise sharply during inflammation, masking true iron deficiency and leading to misdiagnosis or inappropriate treatment.
The Problem: Ferritin’s Double Role
Ferritin is widely used as a screening tool for iron deficiency. Under normal conditions, low ferritin is a reliable indicator of depleted iron stores. However, in the presence of inflammation, infection, or chronic disease, ferritin levels can be elevated even when iron stores are low. This is because inflammatory cytokines—especially IL-6—stimulate ferritin production as part of the body’s acute-phase response.
Key clinical scenarios where this is a problem:
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Chronic infections (e.g., tuberculosis)
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Autoimmune diseases (e.g., rheumatoid arthritis, lupus)
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Cancer or chronic kidney disease
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Obesity and metabolic syndrome
In these settings, a “normal” or even high ferritin does not rule out iron deficiency.
Why CRP Must Be Measured Alongside Ferritin
C-reactive protein (CRP) is another acute-phase protein, but unlike ferritin, it does not reflect iron status. Instead, it is a sensitive marker of systemic inflammation. By measuring CRP alongside ferritin, clinicians can distinguish between elevated ferritin due to increased iron stores and elevated ferritin due to inflammation.
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If both ferritin and CRP are high: Iron deficiency may still be present, especially if transferrin saturation is low or the patient is symptomatic.
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If ferritin is low (<30 ng/mL), even with high CRP: Iron deficiency is very likely, as inflammation rarely drives ferritin this low.
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If ferritin is between 100–300 ng/mL and CRP is elevated: Additional markers such as transferrin saturation (<20%) or newer ratios (see below) are needed to confirm iron deficiency3.
The Ferritin/CRP Ratio: A New Diagnostic Tool
Recent research has shown that the serum ferritin/CRP ratio is a simple and effective way to diagnose iron deficiency in the context of systemic inflammation. A ratio of ≤6 has been shown to accurately predict iron deficiency, even in patients with chronic inflammation or comorbidities.
“The SF/CRP ratio, with a threshold of ≤6, is a simple and effective biomarker for iron deficiency, even in the presence of systemic inflammation or comorbidities, and could potentially replace the complex set of criteria currently recommended by learned societies.”
This approach is especially useful in older adults and those with chronic heart or kidney failure, where traditional markers are often misleading.
International Guidelines: What Do They Say?
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WHO: In individuals with infection or inflammation, a ferritin concentration below 30 μg/L in children and 70 μg/L in adults may be used to indicate iron deficiency. However, the need for and magnitude of inflammation correction depends on the population group and clinical context.
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KDIGO (Kidney Disease: Improving Global Outcomes): In patients with chronic kidney disease, a ferritin threshold of <100 μg/L or transferrin saturation <20% can be considered diagnostic for iron deficiency. If ferritin is 100–300 μg/L, TSAT <20% is required to confirm iron deficiency.
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Recent reviews: Adjusting ferritin cut-offs for inflammation (using CRP and/or α1-acid glycoprotein) can change the estimated prevalence of iron deficiency by up to 25 percentage points in some populations.
AsiaLabs’ Approach: Data You Can Trust
At AsiaLabs, we address these diagnostic challenges by:
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Always recommending Ferritin + CRP combo testing in patients at risk for inflammation-related iron deficiency.
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Using high-sensitivity chemiluminescence for ferritin and immunoturbidimetric assays for CRP, both traceable to WHO reference standards.
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Including interpretive flags based on current KDIGO and WHO guidelines, so clinicians are alerted when results may be confounded by inflammation.
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Offering the ferritin/CRP ratio as part of our reporting for complex cases, providing an additional layer of diagnostic clarity.
Clinical Impact: Avoiding Blind Treatment
Treating anemia without accounting for inflammation can lead to missed diagnoses, unnecessary iron supplementation, or failure to address underlying disease. By integrating CRP with ferritin, clinicians can:
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Detect iron deficiency even when ferritin is “normal” or elevated
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Avoid unnecessary or harmful iron therapy in patients whose ferritin is high due to inflammation, not iron overload
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Target further testing or treatment to those who truly need it
Key Points for Practice
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Never interpret ferritin in isolation when inflammation is suspected.
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Order CRP (and, if possible, transferrin saturation) alongside ferritin in patients with chronic infection, autoimmune disease, cancer, or renal failure.
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Use guideline-based cut-offs and consider the ferritin/CRP ratio for added confidence in complex cases.
Conclusion: See the Whole Picture
Iron studies are only as reliable as the context in which they’re interpreted. In patients with inflammation, ferritin alone can be dangerously misleading. By combining ferritin and CRP—and using ratios and guideline-based cut-offs—clinicians can make more accurate, evidence-based decisions for their patients.
Don’t treat anemia blindly. Use data that reflects the real picture—because your patients deserve nothing less.